The new class of cancer chemotherapeutic agents, "acylated vinylogous carbinolamines", discovered in an earlier phase of this project, provides the focus for this project. Work in progress includes synthesis of new compounds, the study of the chemical and physicochemical properties of key "lead" compounds, and the evaluation of certain biochemical effects produced by these compounds. The new compounds being synthesized include bis-carbamoyloxymethyl derivatives of different five-membered ring heterocycles, of polycyclic ring-fused pyrroles, and of pyrroles and pyrrolizines. The goal is to discover compounds in this class which are superior to existing agents and to define structure-activity requirements for activity, potency, and toxicity. New compounds are also being synthesized to develop agents which show greater water solubility and stability in aqueous solution. Studies of chemical and physico-chemical properties of agents in this class are directed toward evaluation of chemical reactivity and stability, and evaluations of lipid-water distribution properties. These data will be used in the formulation of structure-activity hypotheses. Biochemical studies with key "lead" compounds in the class are also in progress. Studies of DNA intercalation, inhibition of DNA dependent RNA polymerase, as well as in vivo studies of DNA damage and repair will be correlated with chemical studies.